gD is the receptor-binding glycoprotein of herpesviruses (Fusco et al. (2005) Proc. Natl. Acad. Sci. U.S.A. 102:9323). The gD ectodomain is organized in two structurally and functionally differentiated regions. The amino-terminus includes the signal sequence and receptor-binding sites, and the carboxy-terminus includes the pro-fusion domain and the transmembrane domain. gD interacts with two alternative receptors belonging to unrelated protein families, the herpesvirus entry mediator (HVEM) and the nectins (Geraghty et al. (1998) Science 280:1618; Montgomery et al. (1996) Cell 87:427; Cocchi et al. (1998) J. Virol. 72:9992; Warner et al. (1998) Virology 246:179; Lopez et al. (2000) J. Virol. 74:1267). HVEM is expressed on dendritic cells and the B and T lymphocyte attenuator (BTLA) is expressed on activated T and B lymphocytes. The interaction between HVEM and BTLA results in the down-regulation of immune responses.